chrX-103676220-G-A

Variant names:

• chrX-103676220-G-A
• NM_012286.3:c.808C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012286.3(MORF4L2):​c.808C>T​(p.Leu270Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,096,921 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000073 (0 hom. 1 hem.)
• Consequence: MORF4L2 NM_012286.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

Genes affected

MORF4L2 (HGNC:16849): (mortality factor 4 like 2) Predicted to be involved in heterochromatin assembly and histone modification. Predicted to act upstream of or within positive regulation of striated muscle cell differentiation and positive regulation of transcription by RNA polymerase II. Located in nucleolus; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40997615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012286.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORF4L2	NM_012286.3	MANE Select	c.808C>T	p.Leu270Phe	missense	Exon 4 of 4	NP_036418.1	Q15014
	MORF4L2	NM_001142418.2		c.808C>T	p.Leu270Phe	missense	Exon 5 of 5	NP_001135890.1	Q15014
	MORF4L2	NM_001142419.2		c.808C>T	p.Leu270Phe	missense	Exon 4 of 4	NP_001135891.1	Q15014

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORF4L2	ENST00000441076.7	TSL:1 MANE Select	c.808C>T	p.Leu270Phe	missense	Exon 4 of 4	ENSP00000391969.2	Q15014
	MORF4L2	ENST00000360458.5	TSL:2	c.808C>T	p.Leu270Phe	missense	Exon 4 of 4	ENSP00000353643.1	Q15014
	MORF4L2	ENST00000433176.6	TSL:2	c.808C>T	p.Leu270Phe	missense	Exon 4 of 4	ENSP00000415476.2	Q15014

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1096921 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362307

African (AFR) AF: 0.00 AC: 0 AN: 26372

American (AMR) AF: 0.00 AC: 0 AN: 35171

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19340

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 54010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40513

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000951 AC: 8 AN: 841137

Other (OTH) AF: 0.00 AC: 0 AN: 46048

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.24
Sift	Benign	0.11	T
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.30
MutPred		0.55		Loss of stability (P = 0.0351)
MVP		0.92
MPC		1.4
ClinPred		0.92	D
GERP RS		4.6
Varity_R		0.49
gMVP		0.80
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chrX-102931148;